A Drug-drug Interaction Study of Avapritinib and Midazolam

Inclusion Criteria

• •1. Must be ≥18 years of age at the time of signing the informed consent
• •2. Confirmed diagnosis of
• •* metastatic or unresectable KIT mutant GIST that has recurred or progressed after at least 4 lines of prior systemic SOC therapy or the Investigator has determined that treatment with SOC therapy is not appropriate for patients who failed at least 2 lines of prior SOC
• •OR
• •---Non-resectable advance solid tumor with KIT mutation with progression following standard of care treatment.
• •OR
• •---Confirmed diagnosis of recurrent or unresectable CNS tumors including :IDH-mutant astrocytoma, IDH-mutant oligodendroglioma, glioblastoma, H3K27-altered diffuse midline glioma, H3G34-mutant diffuse hemispheric glioma, midline glioma (with unknown H3K27 mutation status) that has failed prior radiation or systemic SOC therapy.
• •3. Must be able to swallow an oral medication
• •4. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• •5. Patient agrees to use contraception consistent with local regulations
• •6. Must provide signed informed consent to participate in the study
• •14. Patients who have a symptomatic nonhealing wound, ulcer, GI perforation, or bone fracture
• •15. Have received organ or allogenic bone marrow or peripheral blood stem cell transplant
• •16. Have known diagnosis of human immunodeficiency virus infection or active viral hepatitis; viral testing is not required
• •17. History of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 14 grams of alcohol). Alcohol consumption will be prohibited 48 hours before screening and throughout the entire the Main Treatment Period
• •18. Use of tobacco- or nicotine-containing products within 3 months of enrollment
• •19. Is a female patient who is unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for until at least 6 weeks after the last dose of study drug. Males who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study drug.
• •20. Is a female patient who is pregnant, as documented by a serum beta human chorionic gonadotropin (β-hCG) pregnancy test consistent with pregnancy obtained within 7 days before the first dose of study drug. Patients with β-hCG values that are within the range for pregnancy but are not pregnant (false positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Females of nonchildbearing potential (postmenopausal for more than 12 months, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) do not require a serum β-hCG test.
• •21. Female who is breastfeeding
• •22. Have a prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the patient, alter the absorption, distribution, metabolism or excretion of the study drugs, or impair the assessment of study results.